Evidence appears to be growing that low selenium status increases the risk of prostate cancer but it is not known whether this applies to all men or only to a sub-population of men. This is an important question given the likely increase in selenium intake that would follow a positive outcome for selenium supplementation in the SELECT Trial and the potential of selenium for toxicity. This study aims to answer this question by genotyping DNA samples for functional selenoprotein single nucleotide polymorphisms (SNPs) that may affect the risk of prostate cancer by lowering the expression level of protective selenoproteins, and thereby effectively conferring differential sensitivity to selenium status. DNA samples from 1360 prostate cancer cases and 859 matched controls, collected during the CAPS (Cancer Prostate in Sweden) Study, will be genotyped for functional SNPs in the GPx1, GPx4 and Sop15 genes by real-time PCR (using an ABI PRISM 7000). Selenium status will be measured in serum samples. Clinical, demographic and other questionnaire information is available on the subjects. Standard statistical techniques will be used to quantify any association between the SNPs and prostate cancer disease risk. If such an association is found, it will implicate not only the functional SNPs themselves as risk factors for prostate cancer but also, through the principle of Mendelian randomisation, the interacting environmental factor itself, selenium status. It would therefore be possible to reduce the incidence of prostate cancer in men from those sub-groups by advising them to optimise their intake of selenium. Reduction of cancer incidence in these sub-groups would reduce the incidence of prostate cancer in the population.